Colorectal CancerPhase 1NCT01189942
A Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer
A Phase 1 study testing OMP-21M18 in people with Colorectal Cancer, run by OncoMed Pharmaceuticals, Inc. at 5 sites in 2 countries.
Trial summary
The purpose of this study is to test the safety and determine the optimal dose of a new drug, OMP-21M18, when given in combination with FOLFIRI, a standard drug treatment for advanced colorectal cancer. Participants must not have had more than one chemotherapy regimen for their metastatic disease. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- OMP-21M18
- How many people
- 18 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Sep 2010to Feb 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have histologically confirmed metastatic colorectal cancer. Subjects may not have received more than 1 prior chemotherapy regimen for their metastatic disease and may not have received irinotecan for treatment of their metastatic disease.
- Age >21 years
- ECOG performance status <2 (see Appendix B)
- Life expectancy of more than 3 months
- Subjects must have normal organ and marrow function as defined below:
- Leukocytes >3.5 x 109/L
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- Absolute neutrophil count >1.25 x 109/L
- Hemoglobin >100 g/L
- Platelets >125 X 109/L
- Total bilirubin <2 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) <5 X institutional ULN
- Alkaline phosphatase <5 X institutional ULN
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within institutional ULN
- Creatinine <1.5 X institutional ULN OR
- Calculated creatinine clearance >60 mL/min using the Cockcroft and Gault formula as follows:
- Creatinine clearance (mL/min) = (140 - age) x ideal body weight [kg] 0.814 x serum creatinine [µmol/L] For women multiply the value from the equation above by 0.85. Where age is in years, weight is in kg, and serum creatinine is in µmol/L
- Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug. Men must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drug. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of study drug, the Investigator should be informed immediately.
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Subjects who meet any of the following criteria will not be eligible for participation in the study:
- Subjects receiving any other investigational agents or anti-cancer therapy.
- Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
- History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
- Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women or nursing women
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- Subjects with known HIV infection
- Known bleeding disorder or coagulopathy
- Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
- Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
- New York Heart Association Classification II, III, or IV (See Appendix D)
- Subjects with a blood pressure of >140/90 mmHg. The BP should be taken using the method described in Section 9.3. Subjects taking antihypertensive medications must be taking ≤ 2 medications to obtain this level of BP control.
- Subjects with tumors that are currently involving the lumen of the gastrointestinal tract
- Subjects with current evidence of cardiac ischemia or heart failure within the last 6 months, subjects who are receiving any medications for cardiac ischemia, subjects with a B-type natriuretic peptide (BNP) value of >200 pg/mL, subjects with a LVEF < 45%, or subjects that have received a total cumulative dose of ≥400 mg/m2 doxorubicin.
- Subjects with ECG evidence of ischemia or ≥ Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Australia4 sites
Sydney Cancer Centre
Camperdown, New South Wales, 2050
Royal Brisbane & Women's Hospital
Herston, Queensland, 4029
Ashford Cancer Centre Research
Kurralta Park, South Australia, 5037
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
About this study
Official title: A Phase 1b Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer
The purpose of this study is to test the safety and determine the optimal dose of a new drug, OMP-21M18, when given in combination with FOLFIRI, a standard drug treatment for advanced colorectal cancer. Participants must not have had more than one chemotherapy regimen for their metastatic disease. OMP-21M18 is a humanized monoclonal antibody (a protein made in the laboratory) developed to target cancer stem cells. The way the body handles OMP-21M18 will also be investigated.
Up to 32 participants, 21 years or older, at up to 6 centres in Australia and New Zealand, will receive intravenous infusions of OMP-21M18 followed by FOLFIRI every two weeks, until disease progression or limited by drug toxicity. After 8 weeks, participants will undergo assessments to determine their disease status. If there is no evidence of disease progression participants will continue to receive infusions of OMP-21M18 and FOLFIRI every second week, until disease progression.
Read the detailed description
Current cancer therapies often produce an initial reduction in tumour size but may not have longterm benefits. One possible explanation for this is the presence cancer cells known as a cancer stem cells. Cancer stem cells represent a small part of the tumour but are believed to be responsible for much of the growth and spread of the cancer. They may also be more resistant to traditional types of therapy, such as chemotherapy and radiation therapy.
The purpose of this study is to test the safety and determine the optimal dose of a new experimental drug, OMP-21M18, when given in combination with FOLFIRI, a chemotherapy regimen consisting of the following three medications: folinic acid (leucovorin), 5fluorouracil and irinotecan. The administration of these three medications is a standard treatment for advanced colorectal cancer. OMP-21M18 is a humanized monoclonal antibody (a protein made in the laboratory) developed to target cancer stem cells. The way the body handles OMP21M18 will also be investigated.
Up to 32 participants, 21 years or older, will be enrolled at up to 6 centres in Australia and New Zealand. Following informed consent and screening, FOLFIRI will be administered once every 14 days (or until toxicity necessitates reducing or delaying a dose). OMP-21M18 will be administered by intravenous (IV) infusion once every 14 days on the same day as FOLFIRI. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants in each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers safe.
Participants will be assessed for disease status every 8 weeks and for safety at every visit and for 30 days after the end of study drug treatment. Safety will be assessed by adverse event monitoring, physical examination, vital signs, blood tests, cardiac monitoring, and participant interview. Response rates, duration of response, time to progression, and survival will be evaluated requiring CT or MRI scans and CEA (tumour marker) levels at baseline and then every 8 weeks. The development of antibodies to treatment will be assessed throughout the study and up to 12 weeks after the end of study drug treatment. During the study blood samples will be taken to assess whether OMP21M18 is producing desired changes to the genes and proteins related to the cancer (biomarkers). The study includes an optional part which will investigate how variations in people's genetic makeup affect their response to medications. This involves the collection of one blood sample just before participants receive their first dose of study treatment. DNA will be extracted from the blood sample for testing.
- Conditions
- Colorectal Cancer
- Being tested
- OMP-21M18
- Keywords
- Phase 1, dose escalation, histologically, confirmed, malignancy, metastatic
- Medical subject headings
- Colorectal Neoplasms, Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OMP-21M18Drug
The first 6 participants will receive OMP21M18 2.5 mg/kg once every other week, the next 6 participants will receive 5 mg/kg once every other week, and the final 6 participants will receive 10 mg/kg once every other week. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants in each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers safe.
What is being measured
The primary outcome is the main question the study is designed to answer.
To the determine the maximum tolerated dose of OMP-21M18 plus FOLFIRI
Measured: Will be done after each patient in dose cohort reaches Day 56
Secondary outcomes (5)
To determine the safety of FOLFIRI plus OMP-21M18 at two dose levels
Measured: Until disease progression plus 30 days after
To determine the rates of immunogenicity of FOLFIRI plus OMP-21M18
Measured: Up until 12 weeks after patient has Disease Progression
To determine population pharmacokinetics
Measured: Until Disease Progression
To determine the exploratory biomarker changes of FOLFIRI plus OMP 21M18
Measured: Until Disease Progression
To determine the preliminary efficacy of FOLFIRI plus OMP-21M18
Measured: Until Disease Progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2010 (estimated)
- Study startSep 2010
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- OncoMed Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novotech (Australia) Pty Limited
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01189942
- Sponsor's protocol ID
- M18-003
- Status last verified
- Sep 2020
- First submitted
- 25 Aug 2010
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01189942
- Acronym / sponsor ID
- M18-003
- Conditions
- Colorectal Cancer
- Keywords
- Phase 1, dose escalation, histologically, confirmed, malignancy, metastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- OncoMed Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Novotech (Australia) Pty Limited
- Study start
- Sep 2010
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 27 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety and determine the optimal dose of a new drug, OMP-21M18, when given in combination with FOLFIRI, a standard drug treatment for advanced colorectal cancer. Participants must not have had more than one chemotherapy regimen for their metastatic disease. OMP-21M18 is a humanized monoclonal antibody (a protein made in the laboratory) developed to target cancer stem cells. The way the body handles OMP-21M18 will also be investigated.
Up to 32 participants, 21 years or older, at up to 6 centres in Australia and New Zealand, will receive intravenous infusions of OMP-21M18 followed by FOLFIRI every two weeks, until disease progression or limited by drug toxicity. After 8 weeks, participants will undergo assessments to determine their disease status. If there is no evidence of disease progression participants will continue to receive infusions of OMP-21M18 and FOLFIRI every second week, until disease progression.
Detailed description
Current cancer therapies often produce an initial reduction in tumour size but may not have longterm benefits. One possible explanation for this is the presence cancer cells known as a cancer stem cells. Cancer stem cells represent a small part of the tumour but are believed to be responsible for much of the growth and spread of the cancer. They may also be more resistant to traditional types of therapy, such as chemotherapy and radiation therapy.
The purpose of this study is to test the safety and determine the optimal dose of a new experimental drug, OMP-21M18, when given in combination with FOLFIRI, a chemotherapy regimen consisting of the following three medications: folinic acid (leucovorin), 5fluorouracil and irinotecan. The administration of these three medications is a standard treatment for advanced colorectal cancer. OMP-21M18 is a humanized monoclonal antibody (a protein made in the laboratory) developed to target cancer stem cells. The way the body handles OMP21M18 will also be investigated.
Up to 32 participants, 21 years or older, will be enrolled at up to 6 centres in Australia and New Zealand. Following informed consent and screening, FOLFIRI will be administered once every 14 days (or until toxicity necessitates reducing or delaying a dose). OMP-21M18 will be administered by intravenous (IV) infusion once every 14 days on the same day as FOLFIRI. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants in each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers safe.
Participants will be assessed for disease status every 8 weeks and for safety at every visit and for 30 days after the end of study drug treatment. Safety will be assessed by adverse event monitoring, physical examination, vital signs, blood tests, cardiac monitoring, and participant interview. Response rates, duration of response, time to progression, and survival will be evaluated requiring CT or MRI scans and CEA (tumour marker) levels at baseline and then every 8 weeks. The development of antibodies to treatment will be assessed throughout the study and up to 12 weeks after the end of study drug treatment. During the study blood samples will be taken to assess whether OMP21M18 is producing desired changes to the genes and proteins related to the cancer (biomarkers). The study includes an optional part which will investigate how variations in people's genetic makeup affect their response to medications. This involves the collection of one blood sample just before participants receive their first dose of study treatment. DNA will be extracted from the blood sample for testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subjects must have histologically confirmed metastatic colorectal cancer. Subjects may not have received more than 1 prior chemotherapy regimen for their metastatic disease and may not have received irinotecan for treatment of their metastatic disease.
- Age >21 years
- ECOG performance status <2 (see Appendix B)
- Life expectancy of more than 3 months
- Subjects must have normal organ and marrow function as defined below:
Key exclusion criteria (15 listed)
- Subjects who meet any of the following criteria will not be eligible for participation in the study:
- Subjects receiving any other investigational agents or anti-cancer therapy.
- Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
- History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
- Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OMP-21M18The first 6 participants will receive OMP21M18 2.5 mg/kg once every other week, the next 6 participants will receive 5 mg/kg once every other week, and the final 6 participants will receive 10 mg/kg once every other week. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants in each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers safe. | Drug | – |
Primary outcome
To the determine the maximum tolerated dose of OMP-21M18 plus FOLFIRI
Time frame: Will be done after each patient in dose cohort reaches Day 56
5 secondary outcomes
To determine the safety of FOLFIRI plus OMP-21M18 at two dose levels
Time frame: Until disease progression plus 30 days after
To determine the rates of immunogenicity of FOLFIRI plus OMP-21M18
Time frame: Up until 12 weeks after patient has Disease Progression
To determine population pharmacokinetics
Time frame: Until Disease Progression
To determine the exploratory biomarker changes of FOLFIRI plus OMP 21M18
Time frame: Until Disease Progression
To determine the preliminary efficacy of FOLFIRI plus OMP-21M18
Time frame: Until Disease Progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OMP-21M18 in people with Colorectal Cancer, run by OncoMed Pharmaceuticals, Inc. at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To the determine the maximum tolerated dose of OMP-21M18 plus FOLFIRI (time frame: Will be done after each patient in dose cohort reaches Day 56). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.